The major outer membrane protein (MOMP) of Chlamydia trachomatis has been identified as a possible immunogen for vaccine development. The objectives of this project are to identify amino acid sequences of MOMP which are surface accessible to immunoglobulin and to determine if these sequences are involved in chlamydia-host cell attachment. Peptides containing sequences of the four variable domains (VD I, II, III, and IV) have been synthesized. These peptides have been used to define surface accessible epitopes. The B serogroup have accessible epitopes on VD II and VD IV; in contrast, the intermediate and the C serogroup have accessible epitopes on VD I and VD IV. Trypsin cleavage of VD II and VD IV of the MOMP of serotype B on the surface of viable EBs results in loss of binding of chlamydiae to HeLa 229 cells. Monoclonal antibodies to VD II and VD IV of serotype B MOMP neutralize infectivity of chlamydiae for HAK cells by preventing attachment. These data indicate that MOMP has a role in attachment of chlamydiae to host cells. MOMP appears to mediate attachment through electrostatic interactions of the hydrophilic surface accessible variable domains and through binding to a hydrophobic pocket in a conserved region of VD IV. The binding to the hydrophobic pocket is dependent upon the conformation of MOMP. Current research is focused on using overlapping synthetic peptides (8 amino acids) attached to pins to identify immunodominant regions of the VDs. Studies using sera from guinea pigs infected with C. psittaci strain GPIC indicate that VD I and VD IV are immunodominant during infection. From these studies, we hope to determine if surface accessible epitopes are also immunodominant during infection.